Porphysomes were recently described in WO 11/044671; nanovesicles formed from porphyrin-phospholipid conjugates that are biocompatible nanoparticles with intrinsic multimodality for biophotonic imaging and therapy.1 Modified phospholipids have proven useful for diverse biotechnology applications including nucleic acid delivery (cationic lipids), diagnostic imaging (radioisotope-chelating lipids), study of biological phenomena (fluorescent lipids), and modulation of pharmacokinetics (PEGylated lipids) and structure (polymerizable lipids).2-4 Phospholipids can be labeled at various positions on their head group or side-chain.5 Head group modification can readily be achieved using the primary amine group of phosphatidylethanolamine. Side-chain modification is less straightforward, but is appropriate for conjugating more hydrophobic ligands while maintaining an amphipathic phospholipid character. In recent years, phospholipids modified with cholesterol, retinoic acid and porphyrin side-chains have been developed that have useful properties for drug delivery, immunological and biophotonic applications.1,6-9 
Synthesis of single side-chain modified phospholipids is often affected by acyl migration. The resulting regioisomers (see FIG. 1A) have similar structures, which make their separation impractical and their detection challenging or impossible using techniques such as HPLC, NMR and mass spectrometry.10 Regioselective phospholipid side-chain modification has been achieved using a number of techniques. Synthesis of modified phospholipids has been performed in multistep reactions using a modified glycerol backbone, with protecting groups sometimes being required.6,9,11 Acylation of lysophospholipids with fatty acid chlorides, imidazoles, anhydrides and thiopyridyl esters has achieved varying degrees of isomeric purity (70% to 99%) and yield (40% to 90%), depending on the method and catalyst.12,13 However, generation of these reactive intermediates may cause degradation and may not produce satisfactory yield or isomeric purity. Direct acylation of carboxylic acids to lysophospholipids with standard coupling agents is a convenient synthetic route, and protocols aiming to reduce acyl migration, such as sonication with glass beads, have been reported.14 